Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci.

UMOD polymorphism rs12917707 is not associated with severe or stable IgA nephropathy in a large Caucasian cohort.

Background: Genetic factors are suspected in the pathogenesis of IgA nephropathy, as well as in the course of IgA nephropathy progression towards end stage renal failure. UMOD polymorphism rs12917707 is known to associate with end stage renal failure of mixed aetiologies.

Methods: We tested a large cohort of Caucasian patients for association of rs12917707 with IgA nephropathy showing a benign, stable course and with IgA nephropathy that progressed toward end stage renal failure.

The podocin mutation R229Q and early recurrence (within the first year) of glomerular disease after renal transplantation.

Background: Podocin is a key protein involved in the pathogenesis of steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis (FSGS) and is characterized by a high rate of early recurrence after renal transplantation (RTx) in children and adults.

Material And Methods: We studied 206 RTx adult recipients: 187 with a diagnosis of glomerular nephropathy, GN (biopsy-proven in 149, clinical in 38), plus 19 with unknown diagnosis as original kidney disease (OKD), the NPHS2 gene polymorphism, G755A, and correlated with the presence of early recurrence of OKD within the first year (proteinuria over 1 g/day and graft-biopsy proven).

Results: The A allele podocin gene mutation frequency was 3.

MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients.

Background: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed.

Methods: We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients.

GFR estimation using standardized cystatin C in kidney transplant recipients.

Background: The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients.

Study Design: Study of diagnostic test accuracy.

Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy.

Mesangial and circulating IgA1 with aberrantly glycosylated hinge region O-glycans characterize IgA nephropathy (IgAN). Unlike healthy individuals, some IgA1 is galactose deficient in patients with IgAN, leaving terminal N-acetylgalactosamine residues in the hinge region exposed. Circulating autoantibodies that recognize such galactose-deficient IgA1 as an autoantigen, or the levels of the autoantigen itself, may allow prediction of disease progression.

Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis.

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.

Comparison of acid and enzymatic methods for inulin dosage: analytical performances and impact on glomerular filtration rate evaluation.

Among issues susceptible to hamper a reliable measurement of inulin clearance, those regarding the dosage of inulin are largely neglected. We have compared the analytical performances of 2 commonly used methods of inulin dosage (one "acid" and one "enzymatic" method) and studied their potential impact on the glomerular filtration rate (GFR) value given by inulin clearance. Repeatability, uncertainty and the beta-expectation limits were evaluated from pre-determined serum and urine pools of inulin.

Single nucleotidic polymorphism 844 A->G of FCAR is not associated with IgA nephropathy in Caucasians.

Background: IgA nephropathy is characterized by a high heterogeneity of clinical expression with 10-30% of patients progressing to end-stage renal failure. The gene of the FcαRI or CD89 presents a single-nucleotide polymorphism responsible for a proinflammatory phenotype of neutrophils in vitro and ex vivo. The aim of our study was to assess whether this CD89 polymorphism 844 A->G is (i) a marker of disease susceptibility and/or (ii) associated with a more severe prognosis.

[Measurement of inulin: development].

Inulin clearance is still considered as the gold standard method to measure glomerular filtration rate. This method has been proposed in thirties by Smith and Shannon but the inulin measurement method still remains complex. Interferences, notably with the glucose, must also be considered.

Predicting the risk for dialysis or death in IgA nephropathy.

For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8).

Creatinine-based GFR predicting equations in renal transplantation: reassessing the tubular secretion effect.

Background: The real utility of blocking the tubular secretion of creatinine with cimetidine in order to ameliorate the prediction of renal graft function is questionable, particularly in the context of an increasing diffusion of the Modification of Diet in Renal Disease (MDRD) study equation. We have compared the impact of cimetidine on the performances of the Cockcroft-Gault (C-G) and MDRD equations in 56 renal transplant patients with an estimated glomerular filter rate (GFR) >30 mL/min/1.73 m(2) for whom true GFR was directly measured by inulin clearance.

Cystatin C-based equations in renal transplantation: moving toward a better glomerular filtration rate prediction?

Creatinine-based glomerular filtration rate (GFR) estimators perform poorly in renal transplant recipients. Cystatin C might be a better alternative to serum creatinine in assessing renal graft function. We compared several cystatin C-based equations with the modification diet renal disease (MDRD) equation in 120 adult renal transplant recipients for whom the GFR was measured by the gold standard inulin clearance.

Antithymocyte globulin (ATG) induction therapy and disease recurrence in renal transplant recipients with primary IgA nephropathy.

Recurrence of primary IgA nephropathy after renal transplantation is clearly a time-dependent event, justifying the use of Kaplan-Meier and Cox regression analyses to sort the significant risk factors. In this retrospective study, we focused on the potential role of induction immunosuppressive therapy. We studied 116 renal transplantation (84 males, 112 cadaveric donors, 95 first grafts, mean age at Tx=46.

IL5RA and TNFRSF6B gene variants are associated with sporadic IgA nephropathy.

Familial clustering and genome-wide linkage scans strongly support a genetic susceptibility to familial IgA nephropathy (IgAN), but genetic factors that predispose to sporadic IgAN are unknown. A high-throughput single nucleotide polymorphism (SNP) association study was conducted using a customized Illumina BeadChip in 732 white patients with biopsy-proven IgAN and 503 control subjects from Canada, France, and Finland. Approximately 93% of 1536 SNPs on the array were tag SNPs from Phase I+II of the HapMap with a minor allele frequency > or =5%, designed to capture the common variants of genes within the critical interval of IGAN1 on chromosome 6q22 and 69 biologic candidate genes for IgAN.

Predicting glomerular filtration rate in kidney transplantation: are the K/DOQI guidelines applicable?

The kidney disease outcomes quality initiative (K/DOQI) guidelines introduced a classification of chronic kidney disease (CKD) based on the level of kidney function. In order to predict the glomerular filtration rate (GFR), they specifically recommended the use of the modification of diet in renal disease (MDRD) study and Cockcroft-Gault (C-G) equations. Since the performance of these estimates has been questioned, we sought to determine whether these recommendations might be applicable in renal transplantation.

G protein beta3 subunit C825T polymorphism in primary IgA nephropathy.

Background: The T allele of the G protein beta3 subunit (GNB3) C825T polymorphism has been associated with increased signal transduction, increased activity of the kidney Na+/H+ exchanger, and also with late-onset essential hypertension. Hypertension is a strong independent risk factor for progression in IgA nephropathy (IgAN).

Methods: We have studied this polymorphism in a regularly followed cohort of 299 biopsy-proven incident cases of IgAN, collected from 1989 to 1999 [208 males (70%)] and compared the genotypes and alleles distributions to 303 local Caucasian controls matched for the male predominance (214 males).

Assessing renal graft function in clinical trials: can tests predicting glomerular filtration rate substitute for a reference method?

Background: In clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients.